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Majority of Gliadin-Specific T-Cell Clones from Celiac Small Intestinal Mucosa Produce Interferon-γ and Interleukin-4

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Abstract

An abnormal mucosal cell-mediated immune response plays a fundamental role in the pathogenesis of celiac disease. To characterize locally infiltrating T cells, gliadin-specific T-cell clones were isolated from two treated celiac patients. Mucosal biopsies were cultured in vitro for 24 hr with a peptic-tryptic digest (PT) of gliadin. T-cell clones (TCC) were then isolated by limiting dilution. The production of interferon-γ (IFN-γ) and interleukin-4 (IL-4) was evaluated by ELISA in culture supernatants obtained after a short incubation with anti-CD3 and PMA, or with antigen. Twenty-two TCC were specific for gliadin and/or PT. All were CD3+, CD4+, CD8+, TCR αβ+. In one such clone the PT-specific response was inhibited by an anti-DQ, but not by an anti-DR antibody. Of the five gliadin-specific TCC examined, four produced IL-4 and high levels of IFN-γ; the remaining one initially produced only IL-4, but subsequently also IFN-γ. All clones obtained from the celiac mucosa, including the gliadin-specific ones, produced high levels of IFN-γ, in most cases with IL-4. This cytokine profile could explain most of the immunological features of the celiac mucosa.

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REFERENCES

  1. Troncone R, Greco L, Auricchio S: Gluten-sensitive enteropathy. Pediatr Clin North Am 43:355- 373, 1996

    Google Scholar 

  2. Marsh MN: Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity (”celiac sprue” ). Gastroenterology 102:330 - 354, 1992

    Google Scholar 

  3. Al-Dawoud A, Nakshabendi I, Foulis A, Mowat AMcI: Immunohistochemical analysis of mucosal gamma-interferon production in celiac disease. Gut 33:1482- 1486, 1992

    Google Scholar 

  4. Przemioslo R, Kontakou M, Nobili V, Sturgess R, Nelufer G, Ciclitira PJ: Interleukin-6 and tumor necrosis factor-alpha in coeliac disease mucosa detected by immuno-histochemistry and in situhybridisation. Gut 34:S24, 1993

    Google Scholar 

  5. Maiuri L, Picarelli A, De Marco G, Coletta S, Fuccio A, Greco M, Di Giovambattista F, Auricchio S, Londei M: Pattern of cytokine expression by treated coeliac intestinal mucosa upon in vitrogliadin challenge. J Pediatr Gastroenterol Nutr 22:414, 1996

    Google Scholar 

  6. Sturgess R, Kontakou M, Spencer J, Hooper L, Makgopa M, Ciclitira PJ: Detection of interferon-g mRNA in the mucosa of patients with coeliac disease by in situhybridisation. Gut 35:1037- 1040, 1994

    Google Scholar 

  7. Kontakou M, Przemioslo RT, Sturgess RP, Limb AG, Ciclitira PJ: Expression of tumor necrosis factor-α, interleukin-6, and Interleukin-2 mRNA in the jejunum of patients with coeliac disease. Scand J Gastroenterol 30:456 - 463, 1995

    Google Scholar 

  8. Kontakou M, Przemioslo RT, Sturgess RP, Limb GA, Ellis HJ, Day P, Ciclitira PJ: Cytokine mRNA expression in the mucosa of treated patients after wheat peptide challenge. Gut 37:52-57, 1995

    Google Scholar 

  9. Lundin KEA, Scott H, Hansen T, Paulsen G, Halstensen TS, Fausa O, Thorsby E, Sollid LM: Gliadin-specific, HLA-DQ (α 1*0501, β 1*0201) restricted T cells isolated from the small intestinal mucosa of coeliac disease patients. J Exp Med 178:187- 196, 1993

    Google Scholar 

  10. Meeuwisse GW: Diagnostic crite ria in coeliac disease. Acta Paediatr Scand 59:461- 463, 1970

    Google Scholar 

  11. Auricchio S, de Ritis G, De Vincenzi M, Occorsio P, Silano V: Effects of gliadin peptides prepared from hexaploid and tetraploid wheat on cultures of intestine from rat fetuses and coeliac children. Pediatr Res 16:1004 - 1010, 1982

    Google Scholar 

  12. Quaranta V, Pellegrino MA, Ferrone S: Serological and immunochemical characte rization of the specificity of four monoclonal antibodies to distinct antigenic determinants expressed on subpopulation of human Ia-like antigens. J Immunol 126:548 - 552, 1981

    Google Scholar 

  13. Halstensen TS, Scott H, Fausa O, Brandtzaeg P: Gluten stimulation of coeliac mucosa in vitroinduces activation (CD25) of lamina propria CD4+ T cells and macrophages but no cryptcell hyperplasia. Scand J Immunol 38:581- 590, 1993

    Google Scholar 

  14. Maiuri L, Troncone R, Mayer M, Coletta S, Picarelli A, De Vincenzi M, Pavone V, Auricchio S: In vitroactivities of A-gliadin-related synthetic peptides. Damaging effect on the atrophic coeliac mucosa and activation of mucosal immune response in the treated coeliac mucosa. Scand J Gastroenterol 31:247- 253, 1996

    Google Scholar 

  15. Halstensen TS, Brandtzaeg P: Activated T lymphocytes in the celiac lesion: Nonproliferative activation (CD25) of CD4+-α/β cells in the lamina propria but proliferation (Ki-67) of α/β and γ/ δ cells in the epithelium. Eur J Immunol 23:505- 510, 1993

    Google Scholar 

  16. Lundin KEA, Scott H, Fausa O, Thorsby E, Sollid LM: T cells from the small intestinal mucosa of a DR4, DQ7/DR4, DQ8 celiac disease patient preferentially recognize gliadin when presented by DQ8. Hum Immunol 41:285- 291, 1994

    Google Scholar 

  17. Breese EJ, Kumar P, Farthing MJ, MacDonald TT: Interleukin- 2- and interferon-γ -producing cells in the lamina propria in celiac disease. Dig Dis Sci 39:2243, 1994

    Google Scholar 

  18. Nilsen EM, Lundin KEA, Krajci P, Scott H, Sollid LM, Brandtzaeg P: Gluten specific, HLA-DQ restricted T cells from coeliac mucosa produce cytokines with Th1 or Th0 profile dominated by interferong. Gut 37:766 - 776, 1995

    Google Scholar 

  19. Nilsen EM, Gjertsen HA, Jensen K, Brandtzaeg P, Lundin KEA: Gluten activation of peripheral blood T cells induces a Th0-like cytokine pattern in both coeliac patients and controls. Clin Exp Immunol 103:295- 303, 1996

    Google Scholar 

  20. Ciclitira PJ, Nelufer JM, Evans DJ: The effect of gluten on HLA-DR in the small intestinal epithelium of patients with coeliac disease. Clin Exp Immunol 63:101- 104, 1986

    Google Scholar 

  21. Fais S, Maiuri L, Pallone F, De Vincenzi M, de Ritis G, Troncone R, Auricchio S: Gliadin induced changes in the expression of MHC-class II antigens by human small intestinal epithelium. Organ culture studies with coeliac disease mucosa. Gut 33:472- 475, 1992

    Google Scholar 

  22. Sturgess RP, Macartney JC, Makgoba MW, Hung CH, Haskard DO, Ciclitira PJ: Differential upregulation of intercellular adhesion mole cule-1 in coeliac disease. Clin Exp Immunol 82:489 - 492, 1990

    Google Scholar 

  23. Maiuri L, Picarelli A, Boirivant M, Coletta S, Mazzilli MC, De Vincenzi M, Londei M, Auricchio S: Definition of the initial immunologic modifications upon in vitrogliadin challenge in the small inte stine of coeliac patients. Gastroenterology 110:1368 - 1378, 1996

    Google Scholar 

  24. Przemioslo RT, Lundin KEA, Sollid LM, Nelufer J, Ciclitira PJ: Histological changes in small bowel mucosa induced by gliadin sensitive T-lymphocyte s can be blocked by antiinterferon-γ antibody. Gut 36:857- 863, 1995

    Google Scholar 

  25. Mowat AMcI, Widmer MB: A role for IL-4 in immunologically mediated enteropathy. Clin Exp Immunol 99:65- 69, 1995

    Google Scholar 

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Troncone, R., Gianfrani, C., Mazzarella, G. et al. Majority of Gliadin-Specific T-Cell Clones from Celiac Small Intestinal Mucosa Produce Interferon-γ and Interleukin-4. Dig Dis Sci 43, 156–161 (1998). https://doi.org/10.1023/A:1018896625699

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  • DOI: https://doi.org/10.1023/A:1018896625699

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